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- 저자 : Yasuhiko Igawa (검색결과 3 건)
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Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder
Yasuhiko Igawa,Naoki Aizawa,Yukio Homma 대한비뇨의학회 2010 Investigative and Clinical Urology Vol.51 No.12
In the present review article, we present an overview of beta-adrenoceptor (b-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the b3-AR, the in vivo effect of b3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of b3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of b3-AR mRNA in human bladder, constituting 97% of total b-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the b3-ARs. Moreover, the presence of b1-, b2-, and b3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial b-ARs results in the release of nitric oxide and an unknown substance inhibiting detrusor contractions from the urothelium. Intravenous application of CL316,243, a selective b3-AR agonist, in rats selectively inhibits mechano-sensitive Ad-fiber activity of the primary bladder afferents. A number of selective b3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the b3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The b3-AR agonists act to facilitate bladder storage function probably through at least two mechanisms: first, direct inhibition of the detrusor, and second, inhibition of bladder afferent neurotransduction.
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Pathophysiology of the underactive bladder
Naoki Aizawa,Yasuhiko Igawa 대한비뇨의학회 2017 Investigative and Clinical Urology Vol.58 No.-
Underactive bladder (UAB), which has been described as a symptom complex suggestive of detrusor underactivity, is usually characterized by prolonged urination time with or without a sensation of incomplete bladder emptying, usually with hesitancy, reduced sensation on filling, and slow stream often with storage symptoms. Several causes such as aging, bladder outlet obstruction, diabetes mellitus, neurologic disorders, and nervous injury to the spinal cord, cauda equine, and peripheral pelvic nerve have been assumed to be responsible for the development of UAB. Several contributing factors have been suggested in the pathophysiology of UAB, including myogenic failure, efferent and/or afferent dysfunctions, and central nervous system dysfunction. In this review article, we have described relationships between individual contributing factors and the pathophysiology of UAB based on previous reports. However, many pathophysiological uncertainties still remain, which require more investigations using appropriate animal models.
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Taguchi, Satoru,Fukuhara, Hiroshi,Kakutani, Shigenori,Takeshima, Yuta,Miyazaki, Hideyo,Suzuki, Motofumi,Fujimura, Tetsuya,Nakagawa, Tohru,Igawa, Yasuhiko,Kume, Haruki,Homma, Yukio Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24
Background: Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Materials and Methods: We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Results: Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ${\geq}9$ and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ${\geq}9$ was an independent predictor of cancer-specific death. Conclusions: Pathologic GS ${\geq}9$ and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ${\geq}9$ was an indispensable condition for bone metastasis, which may imply that patients with GS ${\leq}8$ on adjuvant ADT are unlikely to develop bone metastasis.
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